Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention.

BACKGROUND: Antibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes. METHODS: A prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment. RESULTS: Across a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic allergy report. The highest rate of penicillin allergy de-labelling was demonstrated in patients who were referred for an inpatient oral rechallenge with 95.2% (n = 21) successfully having their penicillin AAL removed. From the 22 patients with Type A reactions, 63.6% had their penicillin AAL removed. We demonstrated a significant decrease in the prescribing of restricted antibiotics (defined as third- or fourth-generation cephalosporins, fluoroquinolones, glycopeptides, carbapenems, piperacillin/tazobactam, lincosamides, linezolid or daptomycin) in patients reviewed (pre 42.5% versus post 17.9%, P = 0.0002). CONCLUSIONS: A pharmacist-led AMS penicillin allergy de-labelling ward round reduced penicillin AALs and the prescribing of restricted antibiotics. This model could be implemented at other hospitals with existing AMS programmes.

Is Aerosolized Pentamidine for Pneumocystis Pneumonia Prophylaxis in Renal Transplant Recipients Not as Safe as We Might Think?

Outbreaks ofPneumocystispneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.

Antimicrobial allergy 'labels' drive inappropriate antimicrobial prescribing: lessons for stewardship.

BACKGROUND: The presence of antimicrobial allergy designations ('labels') often substantially reduces prescribing options for affected patients, but the frequency, accuracy and impacts of such labels are unknown. METHODS: The National Antimicrobial Prescribing Survey (NAPS) is an annual de-identified point prevalence audit of Australian inpatient antimicrobial prescribing using standardized definitions of guideline compliance, appropriateness and indications. Data were extracted for 2 years (2013-14) and compared for patients with an antimicrobial allergy label (AAL) and with no AAL (NAAL). RESULTS: Among 21 031 patients receiving antimicrobials (33 421 prescriptions), an AAL was recorded in 18%, with inappropriate antimicrobial use significantly higher in the AAL group versus the NAAL group (OR 1.12, 95% CI 1.05-1.22, P < 0.002). Patterns of antimicrobial use were significantly influenced by AAL, with lower ß-lactam use (AAL versus NAAL; OR 0.47, 95% CI 0.43-0.50, P < 0.001) and higher quinolone (OR 2.07, 95% CI 1.83-2.34, P < 0.0001), glycopeptide (OR 1.59, 95% CI 1.38-1.83, P < 0.0001) and carbapenem (OR 1.74, 95% CI 1.43-2.13, P < 0.0001) use. In particular, among immunocompromised patients, AAL was associated with increased rates of inappropriate antimicrobial use (OR 1.68, 95% CI 1.21-2.30, P = 0.003), as well as increased use of quinolones (OR 1.88, 95% CI 1.16-3.03, P = 0.02) and glycopeptides (OR 1.82, 95% CI 1.17-2.84, P = 0.01). CONCLUSIONS: AALs are common and appear to be associated with higher rates of inappropriate prescribing and increased use of broad-spectrum antimicrobials. Improved accuracy in defining AALs is likely to be important for effective antimicrobial stewardship (AMS), with efforts to 'de-label' inappropriate AAL patients a worthwhile feature of future AMS initiatives.

Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis?

BACKGROUND: Multidrug-resistant gram-negative bacterial (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating transrectal ultrasound (TRUS)-guided prostate biopsy. Fluoroquinolone-based regimens, once the mainstay of many protocols, are increasingly ineffective. Fosfomycin has reasonable in vitro and urinary activity (minimum inhibitory concentration breakpoint ≤64 µg/mL) against MDR-GNB, but its prostatic penetration has been uncertain, so it has not been widely recommended for the prophylaxis or treatment of MDR-GNB prostatitis. METHODS: In a prospective study of healthy men undergoing a transurethral resection of the prostate for benign prostatic hyperplasia, we assessed serum, urine, and prostatic tissue (transition zone [TZ] and peripheral zone [PZ]) fosfomycin concentrations using liquid chromatography-tandem mass spectrometry, following a single 3-g oral fosfomycin dose within 17 hours of surgery. RESULTS: Among the 26 participants, mean plasma and urinary fosfomycin levels were 11.4 ± 7.6 µg/mL and 571 ± 418 µg/mL, 565 ± 149 minutes and 581 ± 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 ± 4.9 µg/g (range, 0.7-22.1 µg/g), with therapeutic concentrations detectable up to 17 hours following the dose. The mean prostate to plasma ratio was 0.67 ± 0.57. Mean concentrations within the TZ vs PZ prostate regions varied significantly (TZ, 8.3 ± 6.6 vs PZ, 4.4 ± 4.1 µg/g; P = .001). Only 1 patient had a mean prostatic fosfomycin concentration of <1 µg/g, whereas the majority (70%) had concentrations ≥4 µg/g. CONCLUSIONS: Fosfomycin appears to achieve reasonable intraprostatic concentrations in uninflamed prostate following a single 3-g oral dose, such that it may be a potential option for prophylaxis pre-TRUS prostate biopsy and possibly for the treatment of MDR-GNB prostatitis. Formal clinical studies are now required.

Impact of vanB vancomycin-resistant enterococcal bacteraemia analysed as a time-varying covariate on length of hospital stay.

The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length of stay (LOS) in hospital, after adjusting for the time-varying nature of enterococcal bacteraemia (variable onset of bacteraemia post-admission), is unknown. Survival analyses (time-varying Cox and competing risks regression) were performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin-susceptible enterococci bacteraemia patients to determine the factors associated with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia, intensive-care-unit admission, Charlson co-morbidity index score ⩾4, and an increase in the time to receive appropriate antibiotics were associated with prolonged LOS. Competing risks regression which accounts for the influence of in-patient mortality on the ability to observe the event discharge alive from hospital suggests that, vanB VRE bacteraemia was not significantly associated with prolonged LOS. For the first time, the rate of discharge from hospital in patients with vanB VRE bacteraemia has been quantified.

Electronic estimations of renal function are inaccurate in solid-organ transplant recipients and can result in significant underdosing of prophylactic valganciclovir.

In a prospective study of solid-organ transplant recipients (n = 22; 15 hepatic and 7 renal) receiving valganciclovir for cytomegalovirus (CMV) prophylaxis, electronic estimation of glomerular filtration rate (eGFR) underestimated the true GFR (24-h urine creatinine clearance) by >20% in 14/22 (63.6%). Its use was associated with inappropriate underdosing of valganciclovir, while the Cockroft-Gault equation was accurate in 21/22 patients (95.4%). Subtherapeutic ganciclovir levels (≤ 0.6 mg/liter) were common, occurring in 10/22 patients (45.4%); 7 had severely deficient levels (<0.3 mg/liter).

Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency.

BACKGROUND: . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. METHODS: Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women. RESULTS: Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20; P= .001; mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L; P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). CONCLUSIONS: Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.

A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection.

We assessed the in vivo efficacy of surgical and N95 (respirator) masks to filter reverse transcription-polymerase chain reaction (RT-PCR)-detectable virus when worn correctly by patients with laboratory-confirmed acute influenza. Of 26 patients with a clinical diagnosis of influenza, 19 had the diagnosis confirmed by RT-PCR, and 9 went on to complete the study. Surgical and N95 masks were equally effective in preventing the spread of PCR-detectable influenza.

Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA.

Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA; including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [>or=0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 microg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates; the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59; P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively; P < 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42; P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.

Comparison of the Xpert methicillin-resistant Staphylococcus aureus (MRSA) assay, BD GeneOhm MRSA assay, and culture for detection of nasal and cutaneous groin colonization by MRSA.

Detection of methicillin (meticillin)-resistant Staphylococcus aureus colonization was assessed using combined nose and groin swabs in two commercial PCR assays (the Xpert MRSA assay and the BD GeneOhm MRSA assay). Compared to routine culture, both had similar sensitivities (87.0% versus 84.8%, respectively) and specificities (93.8% versus 92.7%, respectively). Combined PCR assays provide a rapid and more-complete assessment of colonization at a cost similar to that of single-site analysis.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Improved detection of vanB2-containing enterococcus faecium with vancomycin susceptibility by Etest using oxgall supplementation.

We have isolated a number of vanB-containing Enterococcus faecium isolates on bile esculin screening agar containing 6 mg/liter vancomycin, which on subsequent susceptibility testing using Etest have repeatedly demonstrated vancomycin MICs of

Acute Flaccid Paralysis: The New, The Old, and The Preventable.

Acute flaccid paralysis (AFP) has a changing epidemiology with ongoing polio outbreaks and emerging causes such as nonpolio enteroviruses and West Nile virus (WNV). We report a case of AFP from the Horn of Africa that was initially classified as probable polio but subsequently found to be due to WNV.

Optimum treatment of staphylococcal infections.

Serious staphylococcal infections remain a significant clinical problem despite advances in antibacterial therapy. Resistance to penicillin is common and methicillin-resistant staphylococci have become troublesome nosocomial pathogens in many institutions. Penicillinase-resistant penicillins (e.g. flucloxacillin, cloxacillin and oxacillin) are the preferred drugs for all methicillin-susceptible staphylococcal infections, although first generation cephalosporins, beta-lactam/beta-lactamase inhibitor combinations, clindamycin, and occasionally erythromycin and cotrimoxazole (trimethoprim/sulfamethoxazole) are alternatives. Serious infections due to methicillin-resistant staphylococci should be treated with parenteral vancomycin. Teicoplanin, where available, is a suitable alternative. Rifampicin, fusidic acid and some fluoroquinolones may be useful oral alternatives, although resistance develops rapidly if they are used as single agents. Cotrimoxazole and minocycline have also proven useful when strains are susceptible. Staphylococcal toxic shock syndrome often requires aggressive resuscitation and anti-staphylococcal therapy for generally 10 to 14 days. Staphylococcus aureus bacteraemia remains a life-threatening condition which, in all but one-third of cases, is associated with an underlying septic focus such as endocarditis, osteomyelitis or occult abscess. Differentiating between complicated and uncomplicated bacteraemia is critical to define the appropriate treatment regimen. Serious staphylococcal sepsis such as endocarditis and acute osteomyelitis generally requires prolonged (4 to 6 weeks) antibiotic treatment. Coagulase-negative staphylococci are the commonest cause of prosthetic device infection, and generally require prolonged therapy with an agent to which they have proven to be sensitive, e.g. a penicillinase-resistant penicillin or vancomycin. Removal of infected foreign or prosthetic material, and drainage of deep collections remain a critical aspect of all therapy.

The prevalence of fecal colonization with VRE among residents of long-term-care facilities in Melbourne, Australia.

A point-prevalence survey performed among residents of eight nursing homes in Melbourne, Australia, found a rate of fecal VRE colonization of 3.1% (9/292; 95% confidence interval, 1.1-5.1), all vanB Enterococcusfaecium. This is a higher rate than in the general community (3.1% vs 0.2%). Many residents (16%) had been inpatients in acute-care hospitals in the previous 3 months.

Diabetic foot infections. Antimicrobial therapy.

Pedal infection in diabetic patients is both a common and potentially disastrous complication that can progress rapidly to irreversible septic gangrene necessitating amputation of the foot. The choice of optimal antibiotic therapy depends on an accurate assessment of sepsis severity, reliable microbiologic data, and consideration of host factors, such as renal and vascular impairment. Empiric broad-spectrum antibiotic regimens are generally preferred because of the polymicrobial nature of most pedal infections. Mild infections may be treated as an outpatient with oral antibiotics and close clinical review while moderate/severe (limb-threatening) and severe (life-threatening) infections require resection of necrotic tissue, parenteral broad-spectrum antibiotic therapy, and in some cases, lower limb revascularization once sepsis has been controlled. Pedal osteomyelitis frequently requires prolonged antibiotic therapy or resection of involved bone. In this article, treatment trials are reviewed and suitable antibiotic regimens commensurate with the severity of infection are proposed.